Acapella: Hypogammaglobulinemia and JCV Status in Ocrelizumab-Treated Patients, Year Five Data

Background: Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody approved for the treatment of relapsing remitting (RRMS) and primary progressive multiple sclerosis (PPMS). During the phase III trials, 1.5% of patients developed low immunoglobulin G (IgG) values after 2-3 years of OCR treatment. JCV antibody index was not studied during the phase III trials. The impact of long-term B-cell suppression on IgG levels and JCV index is unknown.

Objectives: As part of the ACAPELLA trial, a prospective study with a primary objective of assessing OCR-associated adverse events (AEs) in a real-world MS population, we sought to evaluate the impact of OCR treatment on immunoglobulin levels and JCV index.

Methods: The study includes all subjects receiving OCR at the Elliot Lewis Center followed prospectively since March 2017. Subjects are monitored for occurrence of infections and other serious adverse events (SAEs) and have biannual assessments of serum immunoglobulin levels and JCV antibody index.

Results: As of December 31, 2021, 346 subjects with baseline IgG levels were enrolled. 269 subjects completed 3 cycles of OCR, 233 subjects completed 4 cycles, 197 subjects completed 5 cycles, 149 subjects completed 6 cycles, 119 subjects completed 7 cycles, 84 subjects completed 8 cycles, and 40 subjects completed 9 cycles. Fifteen patients (3%) with baseline normal IgG had at least one laboratory value with low IgG. Only 8 patients (2%) developed persistent hypogammaglobulinemia.

Fifteen subjects (4%) had IgG levels below the lower limit of normal (LLN) at baseline. Eleven of 15 patients had subsequent data to analyze. All 11 subjects had IgG levels that remained below or near the LLN.

Three-hundred and forty-three subjects had a baseline JCV index. One-hundred and twenty (35%) had an index <0.4, 91 (27%) were between 0.4-1.5, and 133 (39%) were >1.5. In our year-five data, 26 patients (8%) showed a drop in JCV index ≥ 0.5. These JCV index changes were not associated with a corresponding decline in IgG levels.

Conclusions: In this cohort of patients, persistent hypogammaglobulinemia was infrequent and was not associated with an increased risk of infection. Eight percent of patients treated with 2-8 cycles of OCR had a drop in JCV index of ≥ 0.5 with no corresponding change in IgG. Caution should be exercised when interpreting JCV index in patients previously treated with OCR.